Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B.

Søren Skov; Marianne Terndrup Pedersen; Lars Andresen; Per Thor Straten; Anders Woetmann; Niels Odum

doi:10.1158/0008-5472.CAN-05-0599

Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B.

Søren Skov, Marianne Terndrup Pedersen, Lars Andresen, Per Thor Straten, Anders Woetmann, Niels Odum

207 Citations (Scopus)

Abstract

We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.

Original language	English
Journal	Cancer Research
Volume	65
Issue number	23
Pages (from-to)	11136-45
Number of pages	9
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.CAN-05-0599
Publication status	Published - 2005
Externally published	Yes

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Skov, S., Pedersen, M. T., Andresen, L., Straten, P. T., Woetmann, A., & Odum, N. (2005). Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B. Cancer Research, 65(23), 11136-45. https://doi.org/10.1158/0008-5472.CAN-05-0599

Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B. / Skov, Søren; Pedersen, Marianne Terndrup; Andresen, Lars et al.

In: Cancer Research, Vol. 65, No. 23, 2005, p. 11136-45.

Research output: Contribution to journal › Journal article › Research › peer-review

Skov, S, Pedersen, MT, Andresen, L, Straten, PT, Woetmann, A & Odum, N 2005, 'Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B.', Cancer Research, vol. 65, no. 23, pp. 11136-45. https://doi.org/10.1158/0008-5472.CAN-05-0599

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title = "Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B.",

abstract = "We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.",

author = "S{\o}ren Skov and Pedersen, {Marianne Terndrup} and Lars Andresen and Straten, {Per Thor} and Anders Woetmann and Niels Odum",

note = "Keywords: Antibiotics, Antineoplastic; Apoptosis; Cell Line, Tumor; Depsipeptides; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Histocompatibility Antigens Class I; Histone Deacetylases; Humans; Jurkat Cells; Killer Cells, Natural; Neoplasms; T-Lymphocytes",

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doi = "10.1158/0008-5472.CAN-05-0599",

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T1 - Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B.

AU - Skov, Søren

AU - Pedersen, Marianne Terndrup

AU - Andresen, Lars

AU - Straten, Per Thor

AU - Woetmann, Anders

AU - Odum, Niels

N1 - Keywords: Antibiotics, Antineoplastic; Apoptosis; Cell Line, Tumor; Depsipeptides; Enzyme Inhibitors; Glycogen Synthase Kinase 3; Histocompatibility Antigens Class I; Histone Deacetylases; Humans; Jurkat Cells; Killer Cells, Natural; Neoplasms; T-Lymphocytes

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N2 - We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.

AB - We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T cells, and CD8 T cells.

U2 - 10.1158/0008-5472.CAN-05-0599

DO - 10.1158/0008-5472.CAN-05-0599

M3 - Journal article

C2 - 16322264

SN - 0008-5472

VL - 65

SP - 11136

EP - 11145

JO - Cancer Research

JF - Cancer Research

IS - 23

ER -